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Hongmei Luan, Michael Leitges, Rita R. Gupta, Daniel Pacheco, Andres Seidner, Jessica Liggett, Yasuki Ito, Renu Kowluru, Bruce A. Berkowitz; Effect of PKCβ on Retinal Oxygenation Response in Experimental Diabetes. Invest. Ophthalmol. Vis. Sci. 2004;45(3):937-942. doi: 10.1167/iovs.03-1007.
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purpose. To test the hypotheses that, in mice, breathing carbogen (95% O2-5% CO2) oxygenates the retina better than breathing 100% oxygen, the superior hemiretinal oxygenation response to carbogen inhalation is subnormal early in diabetes, and diabetes-induced elevation of retinal protein kinase C (PKC)-β contributes to this pathophysiology.
methods. Retinal oxygenation response (ΔPo 2) was measured using functional magnetic resonance imaging (MRI) and either carbogen or 100% oxygen inhalation challenge in C57BL/6J control (C) mice. Retinal ΔPo 2 during carbogen breathing was also measured in PKCβ knockout (C57BL6-Prkcb1; [KO]), 4 month C57BL/6J diabetic (D), and 4-month diabetic PKCβ KO (D+KO) mice. Retinal PKCβ protein expression was assessed by Western analysis.
results. In C mice, retinal ΔPo 2 during carbogen breathing was significantly greater (P < 0.05) than during oxygen breathing. In D mice, ΔPo 2 during carbogen breathing was significantly lower than normal in the superior, but not the inferior, hemiretina and was normal (P > 0.0 5) in the KO group. In the D+KO mice ΔPo 2 was normal (P > 0.05) only at distances less than 1.5 mm from the optic nerve head. PKCβ expression was elevated in the retina in diabetes (P < 0.05), but was significantly decreased (P < 0.05) in D+KO mice.
conclusions. The present study confirms that, in the mouse, retinal ΔPo 2 patterns during different inhalation challenges or in the presence of diabetes are similar to what has been reported in rats. Diabetes-induced elevation of PKC appears to contribute only focally to subnormal retinal ΔPo 2. This raises the possibility that PKC inhibition therapy may be only regionally effective in treating retinal pathophysiology associated with diabetic retinopathy.
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